HuMax-CD20 i(Ofatumumab) n Follicular Lymphoma (FL) Patients Refractory to Rituximab

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00394836
First received: October 31, 2006
Last updated: December 12, 2013
Last verified: November 2013
  Purpose

A Single-Arm, International, Multi-Center Trial of HuMax-CD20 (Ofatumumab), a Fully Human Monoclonal Anti-CD20 Antibody, in Patients With Follicular Lymphoma Who Are Refractory to Rituximab as Monotherapy or in Combination With Chemotherapy


Condition Intervention Phase
Lymphoma, Follicular
Drug: Ofatumumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Single-arm, International, Multi-center Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20 Antibody, in Patients With Follicular Lymphoma Who Are Refractory to Rituximab as Monotherapy or in Combination With Chemotherapy

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With Objective Response (OR) [ Time Frame: Start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32) ] [ Designated as safety issue: No ]
    OR was assessed by an Independent endpoints Review Committee (IRC) according to the standardized response criteria for Non-Hodgkin's lymphoma. Participants with Complete Response (CR; complete disappearance of all detectable disease), Complete Response unconfirmed (CRu; any residual lymph node/nodal mass >1.5 centimeters [cm] in its longest transverse diameter that regressed >75% compared to baseline), or Partial Response (PR; >=50% decrease in the sum of the product of diameters of indicator lesions) were defined as responders for OR.

  • Number of Participants Classified as Responders and Non-responders for Objective Response (OR) [ Time Frame: 6-month period from the start of treatment. There was a median time of response at Month 5.5 (participants were followed for up to 24 months). ] [ Designated as safety issue: No ]
    Based on OR over a 6-month period from start of treatment, participants were classified as responders/non-responders as follows: participants with CR, CRu, or PR were classified as responders, whereas participants with Stable Disease (SD; achieving less than PR but not consistent with PD), Progressive Disease (PD; 50% increase from nadir in the products of the greatest perpendicular diameters of any previously identified node or appearance of any new node >1 cm), or Not Evaluable (NE) participants were classified as non-responders.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: From start of treatment (Week 0) until Month 24 ] [ Designated as safety issue: No ]
    The duration of response is defined as the time from the initial response (the first visit at which response was observed) to progression or death. For participants who were lost to follow-up, duration of response was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate duration of response.

  • Progression-Free Survival [ Time Frame: From start of treatment (Week 0) until Month 24 ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as the time from randomization until the first radiologically or clinically documented evidence of progression or death due to any cause, if sooner. For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.

  • Time to Next Follicular Lymphoma (FL) Therapy [ Time Frame: From start of treatment (Week 0) until Month 24 ] [ Designated as safety issue: No ]
    Time to next FL (anti-lymphoma) therapy is defined as the time from randomization until the time of first administration of the next anti-lymphoma therapy other than ofatumumab. For participants who were lost to follow-up, the time was censored at the date of the last attended visit at which the endpoint was assessed.

  • Overall Survival [ Time Frame: First dose (Week 0) until 5 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization until death. For participants who are lost to follow-up, overall survival will be censored at the date of the last attended visit at which the endpoint was assessed.

  • Percent Change From Screening (Visit 1) in Tumor Size as Assessed by Radiologist 1 (R1) and Radiologist 2 (R2) at Months 3, 6, 9, 12, 18, and 24 [ Time Frame: Visits 1 (Week -2), 11 (Month 3), 12 (Month 6), 13 (Month 9), 14 (Month 12), 16 (Month 18), and 18 (Month 24) ] [ Designated as safety issue: No ]
    Tumor size was measured by computed tomography (CT) scan and was computed as the sum of product of diameters (SPD) for the indicator lesions. CT scans with contrast of the neck, thorax, abdomen, and pelvis were performed at Screening and during the follow-up period (Month 3, 6, 9, 12, 18, and 24). The change in tumor size from Screening (Visit 1) was presented per Radiologist 1 (R1) and Radiologist 2 (R2). Percent change from Screening (Visit 1, Week -2) = (value at Visits 11, 12, 13, 14, 16, and 18 minus the value at Visit 1 divided by the value at Visit 1) * 100.

  • Percent Change From Baseline (Visit 2) in CD19+ and CD20+ Cells in Peripheral Blood at Visits 11 and 12 [ Time Frame: Visits 2 (Baseline), 11 (Month 3), and 12 (Month 6) ] [ Designated as safety issue: No ]
    CD19 and CD20 are proteins found on the cell surface of B cells, and they can be detected in peripheral blood by flow cytometry. Flow cytometry of peripheral blood was performed for immediate analysis of cells with cluster of differentiation 19 (CD19+) and CD20+. The analysis will be done until a value is reached that is in the normal range. Percent change from Baseline (Visit 2) = (value at Visits 11 and 12 minus the value at Visit 2 divided by the value at Visit 2) * 100.

  • Number of Participants With Conversion and no Conversion of BCL2 Positive to BCL2 Negative in Peripheral Blood [ Time Frame: Screening (Visit 1) until Month 24 (Visit 18) ] [ Designated as safety issue: No ]
    B-cell lymphoma 2 (BCL2) is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. BCL2 mitochondrial ribonucleic acid (mRNA) was measured by polymerase chain reaction (PCR) from peripheral blood. Participants who had no post-screening data were categorized as "Missing."

  • Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 18 (Month 24) [ Time Frame: From first treatment (Visit 2) until Visit 18 (Month 24) ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. A list of AEs experienced in the study at a frequency threshold of 5% can be found in the AE section.

  • Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Visits 1, 12, 13, and 14 [ Time Frame: Visits 1 (Screening), 12 (Month 6), 13 (Month 9), and 18 (Month 24) ] [ Designated as safety issue: No ]
    HAHA are indicators of immunogenicity to ofatumumab. Blood samples were withdrawn from participants at Visits 1, 12, 13, and 18 for analysis of HAHA. Analysis of HAHA was done in batches.

  • Complement (CH50) Levels at Visit 1 and at the End of Infusion at Visit 2 [ Time Frame: Visits 1 (Week -2) and 2 (Week 0) ] [ Designated as safety issue: No ]
    Blood samples were drawn from participants at Visits 1 and 2 for analysis of complement (CH50) levels. Analysis of CH50 was done in batches, and CH50 levels were measured two hours after the end of study medication infusion. Percent change from Screening (Visit 1, Week -2) = (value at Visit 2 minus the value at Visit 1 divided by the value at Visit 1) * 100.

  • Number of Participants Classified as Responders for Fragment C Receptor (FcR) Polymorphism (Poly.) [ Time Frame: From first treatment (Visit 2) until Visit 12 (Month 6) ] [ Designated as safety issue: No ]
    FcR poly. affect the affinity with which FcRs interact with immunoglobulin molecules and are prognostic factors that are indicative of altered responsiveness to treatment and/or survival. A blood sample was drawn at Visit 1 for analysis (done in batches of several samples) of FcR poly. (Fcgamma RIIIa Valine/Phenylalanine genotypes [TT=thymidine/thymidine, TG=thymidine/guanine, GG=guanine/guanine] and Fcgamma RIIa Arginine/Histidine genotypes [AA=adenine/adenine, AG=adenine/guanine, GG=guanine/guanine]). Responders must have met the criteria for CR, CRu, or PR at either Month 3 or Month 6. Fc receptor polymorphisms and C1qA-276 results are not included in this results summary.

  • Ctrough and Cmax at the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; up to 10 months after dose) ] [ Designated as safety issue: No ]
    Cmax is defined as the maximum concentration of drug in plasma samples. Ctrough is defined as the trough plasma concentration (measured concentration at the end of a dosing interval [taken directly before the start of the next infusion]).

  • AUC(0-inf) and AUC(0-168) After the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; up to 10 months after dose) ] [ Designated as safety issue: No ]
    AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-168) is AUC from the start of infusion to 168 hours after the start of the infusion; AUC(0-inf) is AUC from the start of infusion extrapolated to infinity.

  • t1/2 After the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; up to 10 months after dose) ] [ Designated as safety issue: No ]
    t1/2 is defined as terminal half-life, which is the time required for the amount of the drug in the body to decrease by half.

  • CL After the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; up to 10 months after dose) ] [ Designated as safety issue: No ]
    CL is the clearance of drug from plasma, which is defined as the volume of plasma from which drug is removed per unit time.

  • Vss After the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; to up 10 months after dose) ] [ Designated as safety issue: No ]
    Vss is the volume of distribution at steady state of ofatumumab.


Enrollment: 116
Study Start Date: May 2007
Study Completion Date: September 2013
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Ofatumumab
    Eight weekly infusions of ofatumumab. The first infusion of 300mg ofatumunab
    Drug: Ofatumumab
    followed by 7 weekly infusions of 1000mg ofatumumab
Detailed Description:

Patients in the study will be randomized into two dose groups. Patients in each dose group will receive one infusion of 300 mg of HuMax-CD20 followed by 7 weekly infusions of either 500 or 1000 mg of HuMax-CD20. Disease status will be assessed every 3 months until month 24.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Patient with follicular lymphoma grade 1 - 2
  • Refractory to rituximab given as monotherapy or in combination with any chemotherapy or to rituximab given as maintenance treatment following R-chemo, defined as:
  • failure to achieve at least PR to rituximab given as monotherapy or in combination with any chemotherapy; or,
  • disease progression while on rituximab (either given as monotherapy or in combination with any chemotherapy or during rituximab maintenance treatment following R-chemo); or,
  • disease progression in responders within 6 months of the last dose of rituximab (either given as monotherapy or in combination with any chemotherapy or after rituximab maintenance treatment schedule following R-chemo)
  • Tumor verified to be CD20+ positive from excisional lymph node biopsy
  • CT scan in screening phase (based on local evaluation) showing:
  • 2 or more clearly demarcated lesions with a largest diameter ≥ 1.5 cm, or
  • 1 clearly demarcated lesion with a largest diameter ≥ 2,0 cm
  • ECOG Performance Status of 0, 1, or 2
  • Age ≥ 18 years
  • Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out

Exclusion Criteria

  • Previous autologous stem cell transplantation within 6 months
  • Previous allogeneic stem cell transplantation
  • More than 1 previous radio immunotherapy regimen
  • Received radio immunotherapy within 3 months
  • Received any Anti-cancer treatment within 4 weeks
  • Received monoclonal antibodies, other than rituximab within 3 months
  • Patients previously treated with anti-CD20 monoclonal antibodies, other than rituximab
  • Life expectancy less than 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00394836

Locations
United Kingdom
GSK Investigational Site
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00394836     History of Changes
Other Study ID Numbers: 111772, Hx-CD20-405, 111772
Study First Received: October 31, 2006
Results First Received: July 28, 2011
Last Updated: December 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
ofatumumab
rituximab
NHL
CD20
refractory

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 21, 2014